Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease.
Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease.
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DOI：
10.1084/jem.186.2.307
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发表时间：
1997-07-21
影响因子：
15.3
通讯作者：
Tonegawa, S
中科院分区：
文献类型：
--
作者：
Lafaille, J J;Keere, F V;Hsu, A L;Baron, J L;Haas, W;Raine, C S;Tonegawa, S
慢性炎性自身免疫性疾病如多发性硬化症、糖尿病和类风湿性关节炎是由CD 4 + Th 1细胞引起的。由于Th 2细胞以多种方式拮抗Th 1细胞功能，因此认为向Th 2的免疫偏离可以预防或治疗自身免疫性疾病。实验性自身免疫性脑脊髓炎（EAE）是一种脱髓鞘疾病，用作多发性硬化症的模型。使用过继转移系统，我们评估了Th 1和Th 2细胞在EAE中的作用。从髓鞘碱性蛋白（MBP）特异性TCR转基因小鼠体外产生的Th 1和Th 2细胞转移到正常和免疫缺陷小鼠。在短暂的临床前阶段后，Th 1细胞在所有受者中引起EAE。令人惊讶的是，Th 2细胞也在RAG-1 KO小鼠和αβ T细胞缺陷小鼠中引起EAE，尽管是在较长的临床前阶段之后。正常或γδ T细胞缺陷小鼠对Th 2细胞诱导的EAE具有抵抗性。这种疾病的组织病理学特征类似于变态反应过程。此外，疾病诱导的Th 1细胞没有改变coadministration的Th 2细胞在任何收件人。这些发现表明，MBP特异性Th 2细胞有可能诱导EAE，并且由先前活化的Th 1细胞诱导的疾病不能被正常淋巴细胞或先前活化的Th 2细胞预防。
Chronic inflammatory autoimmune diseases such as multiple sclerosis, diabetes, and rheumatoid arthritis are caused by CD4+ Th1 cells. Because Th2 cells antagonize Th1 cell functions in several ways, it is believed that immune deviation towards Th2 can prevent or cure autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease used as a model for multiple sclerosis. Using an adoptive transfer system we assessed the role of Th1 and Th2 cells in EAE. In vitro generated Th1 and Th2 cells from myelin basic protein (MBP)-specific TCR transgenic mice were transferred into normal and immunodeficient mice. Th1 cells caused EAE in all recipients after a brief preclinical phase. Surprisingly, Th2 cells also caused EAE in RAG-1 KO mice and in αβ T cell–deficient mice, albeit after a longer preclinical phase. Normal or γδ T cell–deficient mice were resistant to EAE induced by Th2 cells. The histopathological features of this disease resembled those of an allergic process. In addition, disease induction by Th1 cells was not altered by coadmininstration of Th2 cells in any of the recipients. These findings indicate that MBP-specific Th2 cells have the potential to induce EAE and that the disease induced by previously activated Th1 cells cannot be prevented by normal lymphocytes nor by previously activated Th2 cells.